Brain white matter abnormalities and correlation with severity in amyotrophic lateral sclerosis: An atlas-based diffusion tensor imaging study

Objectives: To assess microstructural alterations in white matter (WM) in amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). Methods: DTI data were collected from 34 subjects (18 patients with ALS and 16 healthy controls). The atlas-based region of interest (ROI) analysis was conducted to assess WM microstructure in ALS by combining intra-voxel metrics, which included fractional anisotropy (FA) and mean diffusivity (MD), and an inter-voxel metric, i.e., local diffusion homogeneity (LDH). Correlation analysis of diffusion values and clinical factors was also performed. Results: ALS group showed a significant FA reduction in bilateral corticospinal tract (CST) as well as right uncinate fasciculus (RUF). The areas with higher MD were situated in right corticospinal tract (RCST), left cingulum hippocampus (LCH), RUF, and right superior longitudinal fasciculus (RSLF). Additionally, ALS patients showed decreased LDH in bilateral anterior thalamic radiation (ATR), bilateral CST and left inferior frontal-occipital fasciculus (LIFOF). Significant correlations were observed between ALSFRS-R (revised ALS Functional Rating Scale) scores or progression rate and FA in bilateral CST, as well as between disease duration and LDH in right CST. Receiver operating characteristic (ROC) analysis revealed the feasibility of employing diffusion metrics along the CST to distinguish two groups (AUC = 0.792-0.868, p < .005 for all). Conclusions: WM microstructural alteration is a common pathology in ALS, which can be detected by both intra- and inter-voxel diffusion metrics. The extent of abnormalities in several WM tracts such as ATR and LIFOF may be better assessed through the inter-voxel diffusion measurement.